Life-threatening paraneoplastic cardiovascular events in ALK-positive anaplastic large cell lymphoma

Abstract

Paraneoplastic hypercholesterolemia has almost exclusively been reported in patients with hepatocellular carcinoma [1] and only in one case of gastric hepatoid adenocarcinoma [2] and one case of renal adenocarcinoma [3] (Table 1). Here, we report extremely high LDL-cholesterol levels and multiple critical cardiovascular events heralding lymphoma diagnosis. A 51-year-old woman with a history of arterial hypertension, hypercholesterolemia, and coronary artery disease presented with rapidly progressive fat-leaking xanthelasma palpebrarum (Fig. 1A) and LDL-cholesterol levels surging from 423 to 1023 mg/dl (=26 mmol/L) despite maximal treatment with atorvastatin, ezetimibe, and proprotein-convertasesubtilisin-kexin type-9 (PCSK9-) inhibitor evolocumab. She experienced multiple acute coronary events, recurrent stent stenosis/occlusions, and rapidly progressing bilateral internal carotid artery stenosis requiring endarterectomy, all within a 5-month period. The patient had intermittent fever, 14 kg weight loss, and rectal bleeding. Laboratory analysis showed C-reactive protein 57 mg/L, erythrocyte sedimentation rate 22 mm/h, iron deficiency anemia, elevated carcinoembryonic antigen 4.8 μg/L, and normal C3, C4, antinuclear, antineutrophil cytoplasmic, and 3-Hydroxyl3-methylglutaryl-coenzyme A (HMGCoA) reductase antibodies. 18F-fluorodeoxyglucose positron emission tomography-computed tomography revealed lymphadenopathy and signs of vasculitis (Fig. 1C). ALK-positive anaplastic large cell lymphoma, null phenotype, Ann-Arbor stage II was diagnosed and curative treatment with 8× CHOEP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 on d1; etoposide 100 mg/m2, d1-3; prednisolone 100 mg d1-5) considered [5]. Concurrent lipapheresis q1w was initiated (MONET®-system, Fresenius, Bad Homburg, Germany). After 3 cycles without doxorubicin because of recurrent unstable coronary artery disease, she obtained a complete response and vasculitis resolved (Fig. 1D). Upon resolution of unstable angina pectoris and LDL-cholesterol decrease to ~200 mg/dl, etoposide was replaced by doxorubicin. After the 5th cycle, the patient developed treatment-refractory hypertension due to acute renal artery stenosis. Chemotherapeutic treatment was aborted, and considering a cumulative doxorubicin dose of only 100mg/m2, consolidating radiotherapy (30 Gy, 15 fractions) was initiated. Now more than 4 years after diagnosis, the patient remains * F. J. Sherida H. Woei-A-Jin [email protected]